Molecular overlap in the regulation of SK channels by small molecules and phosphoinositides.

ABSTRACT: Phosphatidylinositol 4,5-bisphosphate (PIP₂) directly interacts with the small-conductance Ca²⁺-activated K⁺ 2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP₂ binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP₂ to potentiate channel activity. This novel modulation of PIP₂ sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP₂-dependent proteins.

SUBMITTER: Zhang M 

PROVIDER: S-EPMC4563807 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature